JP4465193B2 - リン酸塩輸送インヒビター - Google Patents
リン酸塩輸送インヒビター Download PDFInfo
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- JP4465193B2 JP4465193B2 JP2003578384A JP2003578384A JP4465193B2 JP 4465193 B2 JP4465193 B2 JP 4465193B2 JP 2003578384 A JP2003578384 A JP 2003578384A JP 2003578384 A JP2003578384 A JP 2003578384A JP 4465193 B2 JP4465193 B2 JP 4465193B2
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- 229910019142 PO4 Inorganic materials 0.000 title claims abstract description 67
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 title claims abstract description 67
- 239000010452 phosphate Substances 0.000 title claims abstract description 67
- 239000003112 inhibitor Substances 0.000 title claims description 13
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 80
- 125000003118 aryl group Chemical group 0.000 claims abstract description 54
- 150000001875 compounds Chemical class 0.000 claims abstract description 47
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 39
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract description 37
- 125000003107 substituted aryl group Chemical group 0.000 claims abstract description 28
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 26
- 125000005647 linker group Chemical group 0.000 claims abstract description 24
- 150000001412 amines Chemical class 0.000 claims abstract description 19
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims abstract description 19
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 17
- 150000003568 thioethers Chemical class 0.000 claims abstract description 16
- 125000006575 electron-withdrawing group Chemical group 0.000 claims abstract description 13
- 230000002401 inhibitory effect Effects 0.000 claims abstract description 13
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims abstract description 12
- 125000006245 phosphate protecting group Chemical group 0.000 claims abstract description 11
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 7
- 125000000008 (C1-C10) alkyl group Chemical group 0.000 claims abstract description 3
- -1 1,2-dibromo-ethyl group Chemical group 0.000 claims description 40
- 125000001246 bromo group Chemical group Br* 0.000 claims description 34
- 125000001309 chloro group Chemical group Cl* 0.000 claims description 34
- 125000001424 substituent group Chemical group 0.000 claims description 33
- 125000001931 aliphatic group Chemical group 0.000 claims description 22
- 239000008194 pharmaceutical composition Substances 0.000 claims description 19
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 17
- 150000003839 salts Chemical class 0.000 claims description 17
- 230000005764 inhibitory process Effects 0.000 claims description 13
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 9
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical group NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 claims description 7
- 101100439662 Arabidopsis thaliana CHR5 gene Proteins 0.000 claims description 7
- 229920006395 saturated elastomer Polymers 0.000 claims description 7
- KXDAEFPNCMNJSK-UHFFFAOYSA-N Benzamide Chemical group NC(=O)C1=CC=CC=C1 KXDAEFPNCMNJSK-UHFFFAOYSA-N 0.000 claims description 5
- 229910052736 halogen Inorganic materials 0.000 claims description 5
- 150000002367 halogens Chemical class 0.000 claims description 5
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
- KHBQMWCZKVMBLN-IDEBNGHGSA-N benzenesulfonamide Chemical group NS(=O)(=O)[13C]1=[13CH][13CH]=[13CH][13CH]=[13CH]1 KHBQMWCZKVMBLN-IDEBNGHGSA-N 0.000 claims description 3
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
- 239000003814 drug Substances 0.000 claims description 3
- 125000000466 oxiranyl group Chemical group 0.000 claims description 3
- 125000005543 phthalimide group Chemical group 0.000 claims description 3
- QLNJFJADRCOGBJ-UHFFFAOYSA-N propionamide Chemical group CCC(N)=O QLNJFJADRCOGBJ-UHFFFAOYSA-N 0.000 claims description 3
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 125000003368 amide group Chemical group 0.000 claims 2
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 1
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 99
- 229920000642 polymer Polymers 0.000 description 72
- 239000000243 solution Substances 0.000 description 63
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 57
- 239000000203 mixture Substances 0.000 description 52
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
- 239000007787 solid Substances 0.000 description 35
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 33
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 27
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 27
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 24
- 239000007788 liquid Substances 0.000 description 23
- 239000000725 suspension Substances 0.000 description 21
- 238000000034 method Methods 0.000 description 20
- 239000000047 product Substances 0.000 description 20
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 16
- 239000002253 acid Substances 0.000 description 16
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 15
- IYYIVELXUANFED-UHFFFAOYSA-N bromo(trimethyl)silane Chemical compound C[Si](C)(C)Br IYYIVELXUANFED-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 14
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 14
- 238000002390 rotary evaporation Methods 0.000 description 14
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 14
- 238000011282 treatment Methods 0.000 description 14
- 239000000872 buffer Substances 0.000 description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
- 238000002360 preparation method Methods 0.000 description 12
- 239000002904 solvent Substances 0.000 description 12
- 201000010099 disease Diseases 0.000 description 11
- 238000003756 stirring Methods 0.000 description 11
- 239000006228 supernatant Substances 0.000 description 11
- OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 10
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 10
- 229910052791 calcium Inorganic materials 0.000 description 10
- 239000011575 calcium Substances 0.000 description 10
- 239000012044 organic layer Substances 0.000 description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 9
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
- 238000005119 centrifugation Methods 0.000 description 9
- 230000000968 intestinal effect Effects 0.000 description 9
- 239000000178 monomer Substances 0.000 description 9
- 229910052757 nitrogen Chemical group 0.000 description 9
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 9
- 125000005328 phosphinyl group Chemical group [PH2](=O)* 0.000 description 9
- 239000011541 reaction mixture Substances 0.000 description 9
- 210000002966 serum Anatomy 0.000 description 9
- 125000006850 spacer group Chemical group 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 8
- 208000001647 Renal Insufficiency Diseases 0.000 description 8
- 238000003556 assay Methods 0.000 description 8
- 230000000694 effects Effects 0.000 description 8
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 8
- 201000005991 hyperphosphatemia Diseases 0.000 description 8
- 201000006370 kidney failure Diseases 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 235000009518 sodium iodide Nutrition 0.000 description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 7
- 229930195725 Mannitol Natural products 0.000 description 7
- PUWRRFJWMBAYMQ-UHFFFAOYSA-L [Na+].[Na+].[Na+].CP([O-])([O-])=O Chemical compound [Na+].[Na+].[Na+].CP([O-])([O-])=O PUWRRFJWMBAYMQ-UHFFFAOYSA-L 0.000 description 7
- 230000009102 absorption Effects 0.000 description 7
- 238000010521 absorption reaction Methods 0.000 description 7
- 239000002585 base Substances 0.000 description 7
- 208000020832 chronic kidney disease Diseases 0.000 description 7
- VONWDASPFIQPDY-UHFFFAOYSA-N dimethyl methylphosphonate Chemical compound COP(C)(=O)OC VONWDASPFIQPDY-UHFFFAOYSA-N 0.000 description 7
- 125000000524 functional group Chemical group 0.000 description 7
- 230000001771 impaired effect Effects 0.000 description 7
- 239000000594 mannitol Substances 0.000 description 7
- 235000010355 mannitol Nutrition 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- 239000008188 pellet Substances 0.000 description 7
- 229920002451 polyvinyl alcohol Polymers 0.000 description 7
- 239000000377 silicon dioxide Substances 0.000 description 7
- 150000003384 small molecules Chemical class 0.000 description 7
- 239000011734 sodium Substances 0.000 description 7
- 239000003039 volatile agent Substances 0.000 description 7
- 208000020084 Bone disease Diseases 0.000 description 6
- ABLZXFCXXLZCGV-UHFFFAOYSA-N Phosphorous acid Chemical group OP(O)=O ABLZXFCXXLZCGV-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000539 dimer Substances 0.000 description 6
- 230000004060 metabolic process Effects 0.000 description 6
- 229920002401 polyacrylamide Polymers 0.000 description 6
- 238000000746 purification Methods 0.000 description 6
- SELHAAVPNZRCSB-UHFFFAOYSA-N 11-[dimethoxyphosphorylmethyl(ethoxy)phosphoryl]undec-1-ene Chemical compound COP(=O)(OC)CP(=O)(OCC)CCCCCCCCCC=C SELHAAVPNZRCSB-UHFFFAOYSA-N 0.000 description 5
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical class [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 5
- 102000006335 Phosphate-Binding Proteins Human genes 0.000 description 5
- 108010058514 Phosphate-Binding Proteins Proteins 0.000 description 5
- 239000013543 active substance Substances 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 5
- 239000011230 binding agent Substances 0.000 description 5
- 230000000903 blocking effect Effects 0.000 description 5
- 230000002308 calcification Effects 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 208000022831 chronic renal failure syndrome Diseases 0.000 description 5
- 239000012043 crude product Substances 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 210000001035 gastrointestinal tract Anatomy 0.000 description 5
- 150000004676 glycans Chemical class 0.000 description 5
- 210000003734 kidney Anatomy 0.000 description 5
- 229920000083 poly(allylamine) Polymers 0.000 description 5
- 229920000058 polyacrylate Polymers 0.000 description 5
- 229920000728 polyester Polymers 0.000 description 5
- 229920001282 polysaccharide Polymers 0.000 description 5
- 239000005017 polysaccharide Substances 0.000 description 5
- IMFACGCPASFAPR-UHFFFAOYSA-N tributylamine Chemical compound CCCCN(CCCC)CCCC IMFACGCPASFAPR-UHFFFAOYSA-N 0.000 description 5
- JKMHFZQWWAIEOD-UHFFFAOYSA-N 2-[4-(2-hydroxyethyl)piperazin-1-yl]ethanesulfonic acid Chemical compound OCC[NH+]1CCN(CCS([O-])(=O)=O)CC1 JKMHFZQWWAIEOD-UHFFFAOYSA-N 0.000 description 4
- 108010010803 Gelatin Proteins 0.000 description 4
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- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 4
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
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- 125000002947 alkylene group Chemical group 0.000 description 4
- XXROGKLTLUQVRX-UHFFFAOYSA-N allyl alcohol Chemical compound OCC=C XXROGKLTLUQVRX-UHFFFAOYSA-N 0.000 description 4
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- 238000007152 ring opening metathesis polymerisation reaction Methods 0.000 description 4
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- ZNSIZMQNQCNRBW-UHFFFAOYSA-N sevelamer Chemical compound NCC=C.ClCC1CO1 ZNSIZMQNQCNRBW-UHFFFAOYSA-N 0.000 description 4
- 229910052938 sodium sulfate Inorganic materials 0.000 description 4
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- AXNUIYKEVMRMOZ-UHFFFAOYSA-N 1-[dimethoxyphosphorylmethyl(ethoxy)phosphoryl]decane Chemical compound CCCCCCCCCCP(=O)(OCC)CP(=O)(OC)OC AXNUIYKEVMRMOZ-UHFFFAOYSA-N 0.000 description 3
- NYYLZXREFNYPKB-UHFFFAOYSA-N 1-[ethoxy(methyl)phosphoryl]oxyethane Chemical compound CCOP(C)(=O)OCC NYYLZXREFNYPKB-UHFFFAOYSA-N 0.000 description 3
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- GAWKYKJKVOFTMK-UHFFFAOYSA-N [11-aminoundecyl(hydroxy)phosphoryl]methylphosphonic acid Chemical compound NCCCCCCCCCCCP(O)(=O)CP(O)(O)=O GAWKYKJKVOFTMK-UHFFFAOYSA-N 0.000 description 3
- 239000004480 active ingredient Substances 0.000 description 3
- 229910052782 aluminium Inorganic materials 0.000 description 3
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- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
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- NPGFXTQYCCQUPB-UHFFFAOYSA-N 11-[dimethoxyphosphorylmethyl(ethoxy)phosphoryl]undecan-1-ol Chemical compound COP(=O)(OC)CP(=O)(OCC)CCCCCCCCCCCO NPGFXTQYCCQUPB-UHFFFAOYSA-N 0.000 description 2
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- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- QVCZFLCDKXOIBB-UHFFFAOYSA-N C=CCCCCCCCCCCl(O)(P(O)(O)=O)(=O)=O Chemical compound C=CCCCCCCCCCCl(O)(P(O)(O)=O)(=O)=O QVCZFLCDKXOIBB-UHFFFAOYSA-N 0.000 description 2
- UQXHVIYQCBZGBU-UHFFFAOYSA-N CC(C)OOP(C)(=O)OOC(C)C Chemical compound CC(C)OOP(C)(=O)OOC(C)C UQXHVIYQCBZGBU-UHFFFAOYSA-N 0.000 description 2
- NGYDLKSGFTWXNL-UHFFFAOYSA-N CCOP(Cl)=O Chemical compound CCOP(Cl)=O NGYDLKSGFTWXNL-UHFFFAOYSA-N 0.000 description 2
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- VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 2
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- 108010078791 Carrier Proteins Proteins 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
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Classifications
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/655—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms
- C07F9/65502—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having oxygen atoms, with or without sulfur, selenium, or tellurium atoms, as the only ring hetero atoms the oxygen atom being part of a three-membered ring
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P13/00—Drugs for disorders of the urinary system
- A61P13/12—Drugs for disorders of the urinary system of the kidneys
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/18—Drugs for disorders of the endocrine system of the parathyroid hormones
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/3804—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)] not used, see subgroups
- C07F9/3808—Acyclic saturated acids which can have further substituents on alkyl
- C07F9/3821—Acyclic saturated acids which can have further substituents on alkyl substituted by B, Si, P or a metal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/28—Phosphorus compounds with one or more P—C bonds
- C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
- C07F9/40—Esters thereof
- C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
- C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl
- C07F9/4012—Esters of acyclic acids which can have further substituents on alkyl substituted by B, Si, P or a metal
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
- C07F9/02—Phosphorus compounds
- C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
- C07F9/553—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom
- C07F9/5537—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom having one nitrogen atom as the only ring hetero atom the heteroring containing the structure -C(=O)-N-C(=O)- (both carbon atoms belong to the heteroring)
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F30/00—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal
- C08F30/02—Homopolymers or copolymers of compounds having one or more unsaturated aliphatic radicals, each having only one carbon-to-carbon double bond, and containing phosphorus, selenium, tellurium or a metal containing phosphorus
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F8/00—Chemical modification by after-treatment
- C08F8/40—Introducing phosphorus atoms or phosphorus-containing groups
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- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
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- Chemical & Material Sciences (AREA)
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- General Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
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- Pharmacology & Pharmacy (AREA)
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- Polymers & Plastics (AREA)
- Physical Education & Sports Medicine (AREA)
- Diabetes (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Rheumatology (AREA)
- Hematology (AREA)
- Urology & Nephrology (AREA)
- Endocrinology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Polysaccharides And Polysaccharide Derivatives (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US36594002P | 2002-03-19 | 2002-03-19 | |
| PCT/US2003/008449 WO2003080630A2 (en) | 2002-03-19 | 2003-03-19 | Phosphate transport inhibitors |
Publications (3)
| Publication Number | Publication Date |
|---|---|
| JP2005520864A JP2005520864A (ja) | 2005-07-14 |
| JP2005520864A5 JP2005520864A5 (de) | 2006-05-18 |
| JP4465193B2 true JP4465193B2 (ja) | 2010-05-19 |
Family
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Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2003578384A Expired - Fee Related JP4465193B2 (ja) | 2002-03-19 | 2003-03-19 | リン酸塩輸送インヒビター |
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| Country | Link |
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| US (2) | US7109184B2 (de) |
| EP (1) | EP1485391B1 (de) |
| JP (1) | JP4465193B2 (de) |
| AT (1) | ATE337326T1 (de) |
| AU (1) | AU2003218270A1 (de) |
| DE (1) | DE60307799T2 (de) |
| WO (1) | WO2003080630A2 (de) |
Families Citing this family (16)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6733780B1 (en) | 1999-10-19 | 2004-05-11 | Genzyme Corporation | Direct compression polymer tablet core |
| ATE337326T1 (de) * | 2002-03-19 | 2006-09-15 | Genzyme Corp | Hemmer des phosphattransports |
| US7985418B2 (en) * | 2004-11-01 | 2011-07-26 | Genzyme Corporation | Aliphatic amine polymer salts for tableting |
| AU2012205214B2 (en) * | 2005-09-15 | 2015-05-21 | Genzyme Corporation | Formulation for Amine Polymers |
| EP3000460A1 (de) * | 2005-09-15 | 2016-03-30 | Genzyme Corporation | Beutelformulierung für aminpolymere |
| CN101835500B (zh) * | 2007-08-29 | 2014-05-28 | 吸附剂治疗学公司 | 具有可变抗衡离子含量的吸收性聚合物组合物及其制备方法和用途 |
| WO2018129556A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds and methods for inhibiting nhe-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| SI2384318T1 (en) | 2008-12-31 | 2018-03-30 | Ardelyx, Inc. | MEASURES AND PROCEDURES FOR THE INHIBITION OF ANTIPORT INHIBITED BY NHE IN THE TREATMENT OF DISEASES RELATED TO STRENGTH OF FLAMMABILITY OR TRADEMARITY WITH SOLO, AND THE EMISSION OF GASTROINTESTINAL TREATMENT |
| US20110081413A1 (en) * | 2009-01-22 | 2011-04-07 | Ashok Omray | Pharmaceutical Compositions Comprising Phosphate-Binding Polymer |
| EP3351250A3 (de) | 2009-01-26 | 2018-10-17 | Opko Ireland Global Holdings, Ltd. | Phosphatverwaltung mit kleinen molekülen |
| US8921343B2 (en) * | 2010-03-05 | 2014-12-30 | Duophos | Arylfluorophosphate inhibitors of intestinal apical membrane sodium/phosphate co-transport |
| MX366293B (es) | 2012-08-21 | 2019-07-04 | Ardelyx Inc | Compuestos y metodos para inhibir al antipuerto mediado por nhe en el tratamiento de trastornos asociados con la retencion de fluidos o la sobrecarga de sal y trastornos del tracto gastrointestinal. |
| US10376481B2 (en) | 2012-08-21 | 2019-08-13 | Ardelyx, Inc. | Compounds and methods for inhibiting NHE-mediated antiport in the treatment of disorders associated with fluid retention or salt overload and gastrointestinal tract disorders |
| LT2983667T (lt) | 2013-04-12 | 2019-07-10 | Ardelyx, Inc. | Nhe3 rišantys junginiai ir fosfato pernešimo slopinimo būdai |
| CA3049678A1 (en) | 2017-01-09 | 2018-07-12 | Ardelyx, Inc. | Compounds useful for treating gastrointestinal tract disorders |
| EA201991676A1 (ru) | 2017-01-09 | 2020-01-30 | Арделикс, Инк. | Ингибиторы nhe-опосредованного антипорта |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3632634A (en) * | 1968-08-16 | 1972-01-04 | Ludwig Maier | Phosphorus compounds having the skeleton structure |
| DE1945146A1 (de) * | 1968-09-06 | 1970-03-12 | Monsanto Co | Verfahren zur Herstellung von alpha.omega-Bis-(O.O'-diorganophosphonylmethyl-O-organophosphinyl-alkanen |
| US4806532A (en) * | 1985-10-08 | 1989-02-21 | Mayo Foundation For Medical Education And Research | Inhibition of epithelial phosphate transport |
| IL86951A (en) * | 1987-07-06 | 1996-07-23 | Procter & Gamble Pharma | Methylene phosphonoalkylphosphinates and pharmaceutical preparations containing them |
| CA2007641A1 (en) | 1989-02-01 | 1990-08-01 | Donald S. Karanewsky | Combination of squalene synthetase inhibitor and other type of serum cholesterol reducing agent and method for lowering serum cholesterol using such combination |
| CA2016467A1 (en) | 1989-06-05 | 1990-12-05 | Martin Eisman | Method for treating peripheral atherosclerotic disease employing an hmg coa reductase inhibitor and/or a squalene synthetase inhibitor |
| EP0563730A3 (en) * | 1992-03-28 | 1994-07-27 | Hoechst Ag | Alkenylaminoalkylene phosphonic acid esters and process for the preparation of copolymers comprising alkenylaminoalkylene phosphonates and ethylenic unsaturated compounds |
| US5278153A (en) * | 1992-05-18 | 1994-01-11 | E. R. Squibb & Sons, Inc. | Aryl and heteroaryl (phosphinylmethyl)phosphonate squalene synthetase inhibitors and method |
| JP3526575B2 (ja) | 1993-03-08 | 2004-05-17 | エーザイ株式会社 | ホスホン酸誘導体 |
| US5667775A (en) * | 1993-08-11 | 1997-09-16 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
| US5496545A (en) * | 1993-08-11 | 1996-03-05 | Geltex Pharmaceuticals, Inc. | Phosphate-binding polymers for oral administration |
| US5508342A (en) * | 1994-02-01 | 1996-04-16 | The United States Of America As Represented By The Secretary Of Commerce | Polymeric amorphous calcium phosphate compositions |
| US5618851A (en) * | 1995-02-06 | 1997-04-08 | Arch Development Corp. | Grafted methylenediphosphonate ion exchange resins |
| ATE337326T1 (de) * | 2002-03-19 | 2006-09-15 | Genzyme Corp | Hemmer des phosphattransports |
-
2003
- 2003-03-19 AT AT03714264T patent/ATE337326T1/de not_active IP Right Cessation
- 2003-03-19 AU AU2003218270A patent/AU2003218270A1/en not_active Abandoned
- 2003-03-19 DE DE60307799T patent/DE60307799T2/de not_active Expired - Lifetime
- 2003-03-19 US US10/392,280 patent/US7109184B2/en not_active Expired - Lifetime
- 2003-03-19 EP EP03714264A patent/EP1485391B1/de not_active Expired - Lifetime
- 2003-03-19 WO PCT/US2003/008449 patent/WO2003080630A2/en not_active Ceased
- 2003-03-19 JP JP2003578384A patent/JP4465193B2/ja not_active Expired - Fee Related
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2006
- 2006-05-22 US US11/438,679 patent/US7754200B2/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| WO2003080630A2 (en) | 2003-10-02 |
| US7754200B2 (en) | 2010-07-13 |
| DE60307799T2 (de) | 2007-08-16 |
| ATE337326T1 (de) | 2006-09-15 |
| EP1485391A2 (de) | 2004-12-15 |
| US20060280719A1 (en) | 2006-12-14 |
| JP2005520864A (ja) | 2005-07-14 |
| DE60307799D1 (de) | 2006-10-05 |
| EP1485391B1 (de) | 2006-08-23 |
| WO2003080630A3 (en) | 2003-12-11 |
| US20040019020A1 (en) | 2004-01-29 |
| AU2003218270A8 (en) | 2003-10-08 |
| US7109184B2 (en) | 2006-09-19 |
| AU2003218270A1 (en) | 2003-10-08 |
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